It is proposed to continue our investigations of how inorganic fluoride alters the production of cAMP in various tissues and how fluoride alters glucose metabolism in the intact liver cell. At present we have shown that feeding young rats a fluoride-free diet (less than 0.05 ppm fluoride) and 1 ppm fluoride in the drinking water results in significant increases, compared to rats receiving a fluoride-deficient diet, in the cAMP levels in urine, liver, mandibular gland, tibia, femur, kidney, lung and heart within four weeks. Also that there are changes in the concentration of some of the glycolytic intermediates. There is a significant decrease in 2-phosphoglycerate, 3-phosphoglycerate, pyruvate, and lactate and an increase in phosphoenolpyruvate in the liver of rats fed fluoridated water (1 ppm) compared to rats fed a fluoride-deficient diet. These results suggest that two effects of NaF are an increase in adenylate cyclase activity and a decrease in enolase activity. We plan to extend this study to include the effect of other inorganic fluoride salts, e.g., Na2PO2F, Na2SiF6 and shorter time periods. We also are examining the effects of NaF and Na2PO3F on the production of cAMP, glucose, pyruvate and lactate in hepatocytes isolated from fed and fasted rats. At present we are able to demonstrate that NaF alters the production of the metabolites mentioned above. In general, the inorganic fluoride salts alter liver cell metabolism in s similar manner to that of glucagon.